DESCRIPTION: (Adapted from the applicant's description) This application for the Harvard-wide Specialized Center for Reproduction proposes to bring the neuroendocrine and gonadal control of reproduction in the male. Two of the component of reproduction while the other two will explore the gonadal level as Leydig cell control of steroidogenesis. In Project I, will employ tandem phenotyping and genotyping approaches in patients with idiopathic hypogonadotropic hypogonadism (IHH). This is a human model in which a series of genetic defects result in failure of the neuroendocrine component of sexual maturation. In Project II, Dr. Ursula Kaiser will explore the GnRH of gonadotropic genes using LH-T2 cells which are of gonadotrope origin. In Inhibiting Substance (MIS) upon steroidogenesis using the CYP17 gene as well MIS receptor. In addition, she will chart the developmental expression of this receptor and correlate it with steroidogenesis. In Project IV, Dr. Joel Habener will continue his explorations of the role of cAMP-activated pathways of alternative splicing of the gene encoding of the transcription factor, CREB. He will also explore the role of pituitary adenyl cyclase activating peptide; PACAP, and its alternatively spliced type 1 receptor in the autocrine control of spermatogenesis.